Hepatitis B virus genotype B with G1896A and A1762T/G1764A mutations is associated with hepatitis B related acute-on-chronic liver failure

J Med Virol. 2011 Sep;83(9):1544-50. doi: 10.1002/jmv.22159.

Abstract

The existence of statistical associations between hepatitis B-related acute-on-chronic liver failure and both hepatitis B virus (HBV) genotype and mutations in the basal core promoter (BCP) and precore (PC) regions needs to be confirmed. A total of 322 patients with a chronic HBV infection, including 77 with hepatitis B-related acute-on-chronic liver failure, 109 with hepatocellular carcinoma (HCC) and 136 with chronic hepatitis B (CHB) were enrolled. The HBV genotype and the presence of mutations in the BCP/PC regions were determined by direct sequencing, and the frequencies were compared in the three patient groups. Overall, 198/322 (61.5%) were infected with genotype B and 124/322 (38.5%) with genotype C. Genotype B was significantly more frequent in patients with acute-on-chronic liver failure than CHB (92.2% vs. 60.3%, P < 0.001). As a contrast, genotype C was more common in patients with HCC than CHB (58.7% vs. 39.7%, P = 0.003). In genotype B patients, the A1762T/G1764A, A1846T, and G1896A mutations were significantly more prevalent in patients with acute-on-chronic liver failure than CHB (50.7% vs. 28.0%, P = 0.004; 59.2% vs. 34.1%, P = 0.002; 69.0% vs. 41.5%, P = 0.001, respectively). In multivariate analysis, the risk factors for acute-on-chronic liver failure were genotype B, A1762T/G1764A, and G1896A. In conclusion, CHB patients with genotype B, G1896A, and A1762T/G1764A had a higher tendency to develop liver failure than patients with genotype C. Therefore, HBV genotyping and detecting G1896A and A1762T/G1764A mutations might have important clinical implications as predictive risk factors for hepatitis B-related acute-on-chronic liver failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • DNA, Viral / genetics
  • End Stage Liver Disease / virology*
  • Female
  • Genotype
  • Hepatitis B / pathology
  • Hepatitis B / physiopathology
  • Hepatitis B / virology*
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / pathogenicity
  • Humans
  • Liver Failure, Acute / virology*
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Promoter Regions, Genetic
  • Risk Factors
  • Sequence Analysis, DNA

Substances

  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B e Antigens